尿源性高纯度FSH在控制性促排卵中对IVF-ET结局的影响

Effect of domestic highly purified urinary follicle stimulating hormone on outcomes of in vitro fertilization-embryo transfer in controlled ovarian stimulation

目的 探讨国产尿源性高纯度FSH（HP-FSH,其他名称：丽申宝）在控制性促排卵（COS）中对体外受精（IVF）-胚胎移植（ET）结局的影响.方法 采用回顾性分析方法,按2∶1病历随机抽样方法,抽取全国14个生殖中心2010年9月1日至2011年3月31日间具有IVF和（或）卵母细胞胞质内单精子注射（ICSI）指征并首次接受IVF或ICSI助孕治疗的不孕症患者3178例,其不孕原因包括了除排卵障碍性不孕及子宫因素不孕的所有不孕因素.COS方案为促性腺激素释放激素激动剂（GnRH-a）黄体期长方案,使用长效或短效曲普瑞林降调节,当达到降调节标准（按各生殖中心降调标准）后,开始用促性腺激素（Gn）促排卵,以FSH启动日所用FSH种类的不同分为两组：HP-FSH组1932例和基因重组FSH（rFSH,其他名称：果纳芬）组1246例,根据患者个体情况,FSH启动剂量为150 ～ 300 U,并可根据卵泡发育情况调整剂量,当卵泡发育至直径14 ～ 16 mm时,应用人绝经期促性腺激素（hMC） 150 U.当有3个优势卵泡直径达18 mm时,给予肌内注射尿hCG 5000 ～ 10 000 U或基因重组hCG 250μg,注射后34 ～36 h阴道超声下取卵,按各中心常规进行IVF或ICSI.72 h后进行ET,每例患者移植胚胎数≤3个.主要观察指标为周期出生率,次要观察指标包括临床妊娠率、流产率、着床率以及COS和IVF结局等.结果 （1）两组患者基本特征：患者年龄HP-FSH组为（32±4）岁,rFSH组为（30±4）岁;不孕年限HP-FSH组为（5±4）年,rFSH组为（5±3）年;基础窦卵泡计数（AFC） HP-FSH组为（11±5）个,rFSH组为（13±7）个,上述各项基本特征两组间比较,差异均有统计学意义（P＜0.01）.（2） COS情况：COS方案中Gn用量HP-FSH组为（2348±1011）U,rFSH组为（2022±659）U;获卵数HP-FSH组为（13±6）个,rFSH组为（14±7）个;周期冷冻率HP-FSH组为66.30％（1281/1932）,rFSH组为74.88％（933/1246）;上述各项指标两组比较,差异也均有统计学意义（P＜0.01）.但HP-FSH组和rFSH组着床率[分别为30.49％（1111/3644）、32.45％ （737/2271）]、周期临床妊娠率[分别为41.61％（804/1932）、41.97％ （523/1246）]、周期出生率[分别为34.21％（661/1932）、34.19％（426/1246）]、ET周期临床妊娠率[分别为46.58％（804/1726）、48.47％（523/1079）]、ET周期出生率[分别为38.30％ （661/1726）、39.48％（426/1079）]、流产率[分别为13.6％（109/804）、16.4％ （86/523）]及中重度卵巢过度刺激综合征（OHSS）发生率[分别为5.80％（112/1932）、7.78％（97/1246）]比较,差异均无统计学意义（P＞0.05）.（3）治疗费用：HP-FSH组辅助生殖治疗中Gn费用为（4005±1650）元,rFSH组为（6482±2095）元,两组比较,差异有统计学意义（P＜0.01）.结论 在IVF和（或）ICSI中,使用国产HP-FSH进行COS具有与rFSH等同的临床妊娠率及出生率,而且价格便宜,是一种可供选择的Gn药物.

Objective To investigate the effect of domestic urine-derived high-purity follicle-stimulating hormone （HP-FSH,Lishenbao） on the outcome of in vitro fertilization（IVF） embryo transfer （ET） in controlled ovarian stimulation （COS）.Methods From 1 September 2010 to 31 March 2011,total of 3178 infertility patients from 14 Reproductive Center with IVF or intracytoplasmic sperm injection （ICSI） indications who accepted first IVF or ICSI cycle were studied retrospectively.Their causes of infertility include all infertility factors except ovulatory dysfunction infertility and uterine factor infertility.The only long luteal phase gonadotropin-releasing hormone agonist （GnRH-a） protocol was included.Patients were divided into 2 groups according to the type of follicle-stimulating hormone （FSH） agents used：1932 cases in HP-FSH group and 1246 cases in recombinant FSH （rFSH）group.Patients in both groups were combined with human menopausal gonadotropin （hMG） at doses of 150 U when follicle with diameter reached to 14-16 mm.When 3 dominate follicle with diameter reached 18 mm,hCG at dose of 5000 to 10 000 U orrecombinant hCG at dose of 250 μg was administered by intramuscular injection.After 34 to 36 hours,oocytes were obtained guided by ultrasound,then IVF-ET were underwent in their Reproductive Center.The primary endpoint was comparison of live birth rate between the two groups.The secondary endpoints were comparisons of clinical pregnancy rate,miscarriage rate,and implantation rate,as well as COS and IVF outcome between the two groups.Results （1） There were significantly differences in baseline characteristics of the patients between two groups.The mean age was elder（32 ±4 versus 30 ±4,P ＜0.01）,the infertility duration was longer（5 ±4 versus 5 ± 3,P ＜ 0.01）,and antral follicle count （AFC） was less （11 ± 5 versus 13 ± 7,P ＜ 0.01）in patients of HP-FSH group compared with those in patients of rFSH group.（2） As c ompared with rFSH,the total doses of gonadotropin needed was （2348 ± 1011） U in HP-FSH group versus （2022 ± 659） U in rFSH group,the number of oocytes 13 ± 6 in HP-FSH group aud 14 ±7 in rFSH group,the rate of embryo frozen cycle of 66.30％ （1281/1932） in HP-FSH group and 74.88％（933/1246） in rFSH group,which all reached statistical difference （P ＜0.01）.However,there were no significant different implantation rate [30.49％ （1111/3644） versus 32.45％ （737/2271）] between two groups.The other clinical parameters did not show significant difference,including clinical pregnancy rate per started cycle [41.61％ （804/1932） versus 41.97％ （523/1246）],clinical pregnancy rate per ET cycle [46.58 ％ （804/1726） versus 48.47 ％ （523/1079）],live birth rate per started cycle [34.21％ （661 /1932） versus 34.19％ （426/1246）],live birth rate per ET cycle [38.30％ （661/1726） versus 39.48％（426/1079）],miscarriage rate [13.6％ （109/804） versus 16.4％ （86/523）],and moderate/severe ovarian hyperstimulation syndrome （OHSS） rate [5.80％ （112/1932） versus 7.78％ （97/1246）] （P ＞0.05）.（3） Treatment cost：the cost of gonadotropins needed for the patients in HP-FSH group was lower than that in rFSH group（4005 ± 1650 versus 6482 ± 2095,P ＜ 0.01）.Conclusion In IVF/ICSI treatment cycles,domestic HP-FSH has similar live birth rate and lower financial burden when compared with rFSH.